74
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Phage therapy: An alternative to antibiotics in the age of multi-drug resistance

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The practice of phage therapy, which uses bacterial viruses (phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins, specifically against multidrug-resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage- or antibiotic-based, each have relative advantages and disadvantages; accordingly, many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infections. Although much is still unknown about the interactions between phage, bacteria, and human host, the time to take phage therapy seriously seems to be rapidly approaching.

          Related collections

          Most cited references86

          • Record: found
          • Abstract: found
          • Article: not found

          Antibiotic resistance-the need for global solutions.

          The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. Copyright © 2013 Elsevier Ltd. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy.

            To evaluate the efficacy and safety of a therapeutic bacteriophage preparation (Biophage-PA) targeting antibiotic-resistant Pseudomonas aeruginosa in chronic otitis. Randomised, double-blind, placebo-controlled Phase I/II clinical trial approved by UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Central Office for Research Ethics Committees (COREC) ethical review process. A single specialist university hospital. 24 patients with chronic otitis with a duration of several years (2-58). Each patient had, at the time of entry to the trial, an ear infection because of an antibiotic-resistant P. aeruginosa strain sensitive to one or more of the six phages present in Biophage-PA. Participants were randomised in two groups of 12 treated with either a single dose of Biophage-PA or placebo and followed up at 7, 21 and 42 days after treatment by the same otologist. Ears were thoroughly cleaned on each occasion and clinical and microbiological indicators measured. Physician assessed erythema/inflammation, ulceration/granulation/polyps, discharge quantity, discharge type and odour using a Visual Analogue Scale (VAS). Patients reported discomfort, itchiness, wetness and smell also using a VAS. Bacterial levels of P. aeruginosa and phage counts from swabs were measured initially and at follow-up. At each visit patients were asked about side effects using a structured form. Digital otoscopic images were obtained on days 0 and 42 for illustrative purposes only. Relative to day 0, pooled patient- and physician-reported clinical indicators improved for the phage treated group relative to the placebo group. Variation from baseline levels was statistically significant for combined data from all clinic days only for the phage treated group. Variation from baseline levels was statistically significant for the majority of the patient assessed clinical indicators only for the phage treated group. P. aeruginosa counts were significantly lower only in the phage treated group. No treatment related adverse event was reported. The first controlled clinical trial of a therapeutic bacteriophage preparation showed efficacy and safety in chronic otitis because of chemo-resistant P. aeruginosa.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa

              Increasing prevalence and severity of multi-drug-resistant (MDR) bacterial infections has necessitated novel antibacterial strategies. Ideally, new approaches would target bacterial pathogens while exerting selection for reduced pathogenesis when these bacteria inevitably evolve resistance to therapeutic intervention. As an example of such a management strategy, we isolated a lytic bacteriophage, OMKO1, (family Myoviridae) of Pseudomonas aeruginosa that utilizes the outer membrane porin M (OprM) of the multidrug efflux systems MexAB and MexXY as a receptor-binding site. Results show that phage selection produces an evolutionary trade-off in MDR P. aeruginosa, whereby the evolution of bacterial resistance to phage attack changes the efflux pump mechanism, causing increased sensitivity to drugs from several antibiotic classes. Although modern phage therapy is still in its infancy, we conclude that phages, such as OMKO1, represent a new approach to phage therapy where bacteriophages exert selection for MDR bacteria to become increasingly sensitive to traditional antibiotics. This approach, using phages as targeted antibacterials, could extend the lifetime of our current antibiotics and potentially reduce the incidence of antibiotic resistant infections.
                Bookmark

                Author and article information

                Journal
                World J Gastrointest Pharmacol Ther
                WJGPT
                World Journal of Gastrointestinal Pharmacology and Therapeutics
                Baishideng Publishing Group Inc
                2150-5349
                6 August 2017
                6 August 2017
                : 8
                : 3
                : 162-173
                Affiliations
                Derek M Lin, Henry C Lin, Section of Gastroenterology, New Mexico VA Health Care System, Albuquerque, NM 87108, United States
                Britt Koskella, Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, United States
                Henry C Lin, Department of Medicine, University of New Mexico, Albuquerque, NM 87131, United States
                Author notes

                Author contributions: All authors contributed equally to this work with regard to the scope of the subject, the literature review and analysis, drafting, revision, editing, and final approval of the manuscript.

                Correspondence to: Henry C Lin, MD, Section of Gastroenterology, New Mexico VA Health Care System, 1501 San Pedro SE, Albuquerque, NM 87108, United States. helin@ 123456salud.unm.edu

                Telephone: +1-505-2561711-4552

                Article
                jWJGPT.v8.i3.pg162
                10.4292/wjgpt.v8.i3.162
                5547374
                28828194
                9e223500-ec97-4e33-94cf-7ff13959a90b
                ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.

                Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 2 November 2016
                : 13 May 2017
                : 30 May 2017
                Categories
                Review

                bacteriophage,bacteriophage therapy,phage,phage therapy,endolysin,lysin,multidrug resistance,antibiotic resistance,phage safety,methicillin-resistant staphylococcus aureus

                Comments

                Comment on this article